title: Plasma lipid profiling shows similar associations with prediabetes and type 2 diabetes.
abstract: The relationship between lipid metabolism with prediabetes (impaired fasting glucose and impaired glucose tolerance) and type 2 diabetes mellitus is poorly defined. We hypothesized that a lipidomic analysis of plasma lipids might improve the understanding of this relationship. We performed lipidomic analysis measuring 259 individual lipid species, including sphingolipids, phospholipids, glycerolipids and cholesterol esters, on fasting plasma from 117 type 2 diabetes, 64 prediabetes and 170 normal glucose tolerant participants in the Australian Diabetes, Obesity and Lifestyle Study (AusDiab) then validated our findings on 1076 individuals from the San Antonio Family Heart Study (SAFHS). Logistic regression analysis of identified associations with type 2 diabetes (135 lipids) and prediabetes (134 lipids), after adjusting for multiple covariates. In addition to the expected associations with diacylglycerol, triacylglycerol and cholesterol esters, type 2 diabetes and prediabetes were positively associated with ceramide, and its precursor dihydroceramide, along with phosphatidylethanolamine, phosphatidylglycerol and phosphatidylinositol. Significant negative associations were observed with the ether-linked phospholipids alkylphosphatidylcholine and alkenylphosphatidylcholine. Most of the significant associations in the AusDiab cohort (90%) were subsequently validated in the SAFHS cohort. The aberration of the plasma lipidome associated with type 2 diabetes is clearly present in prediabetes, prior to the onset of type 2 diabetes. Lipid classes and species associated with type 2 diabetes provide support for a number of existing paradigms of dyslipidemia and suggest new avenues of investigation.
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Meikle
authors.forename: Gerard
authors.initials: G
authors.lastname: Wong
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Barlow
authors.forename: Jacquelyn M
authors.initials: JM
authors.lastname: Weir
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Greeve
authors.forename: Gemma L
authors.initials: GL
authors.lastname: MacIntosh
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Comuzzie
authors.forename: Michael C
authors.initials: MC
authors.lastname: Mahaney
authors.forename: Adam
authors.initials: A
authors.lastname: Kowalczyk
authors.forename: Izhac
authors.initials: I
authors.lastname: Haviv
authors.forename: Narelle
authors.initials: N
authors.lastname: Grantham
authors.forename: Dianna J
authors.initials: DJ
authors.lastname: Magliano
authors.forename: Jeremy B M
authors.initials: JB
authors.lastname: Jowett
authors.forename: Paul
authors.initials: P
authors.lastname: Zimmet
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Curran
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.forename: Jonathan
authors.initials: J
authors.lastname: Shaw
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011236:Prediabetic State / Q000097:blood*
chemical_list: D001786:Blood Glucose; D008055:Lipids